A Phase I/II Study of Revlimid (Lenalidomide) in Combination With Vidaza (Azacitidine) in Patients With Advanced Myelodysplastic Syndrome (MDS)
- Determine the maximum tolerated dose and dose-limiting toxicity of lenalidomide and
azacitidine in patients with advanced myelodysplastic syndromes (MDS).
- Review clinical outcomes, as defined by the International Working Group criteria, in
patients treated with this regimen.
- Determine time to transformation to acute myeloid leukemia or death in patients treated
with this regimen.
- Determine time to relapse after achieving complete or partial remission in patients
treated with this regimen.
- Determine time to disease progression in patients treated with this regimen.
- Determine the effect of this regimen on hematologic status (including peripheral blood
counts and the need for platelet and/or red blood cell transfusions) in these patients.
OUTLINE: This is an open-label, multicenter, dose-escalation study.
Patients receive oral lenalidomide once daily on days 1-14 or days 1-21 and azacitidine
subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days
for up to 7 courses in the absence of relapse (after achieving complete or partial
remission), disease progression, or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses and/or increasing dosing frequencies of
lenalidomide and azacitidine until the maximum tolerated dose (MTD) is determined or the
sixth dose level is reached, whichever occurs first. The MTD is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during
the first course of therapy.
After completion of study treatment, patients are followed annually.
PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
PHASE I: Maximum tolerated dose of lenalidomide and azacitidine
Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group.
After 1 courses (1 months)
Mikkael A. Sekeres, MD, MS
The Cleveland Clinic
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida||Tampa, Florida 33612|
|University of California at Los Angeles||Los Angeles, California 90095|
|Cleveland Clinic Taussig Cancer Instititute, Case Comprehensive Cancer Center||Cleveland, Ohio 44195|